Our hope is that this study will contribute to the global effort towards comprehending why people with these mutations get the disease more frequently, or at a younger age
Patrick Flagmeier
In a new study, a team of academics at the Centre for Misfolding Diseases, in the Department of Chemistry at the University of Cambridge, show that tiny changes in the amino acid sequence of the protein alpha-synuclein can have a dramatic effect on microscopic processes leading to its aggregation that may occur in the brain, eventually resulting in someone being diagnosed with Parkinson’s Disease.
Alpha-synuclein is a protein made up of 140 amino acids, and under normal circumstances plays an important part in helping with the smooth flow of chemical signals in the brain.
Parkinson’s Disease is thought to arise because, for reasons researchers still do not fully understand, the same protein sometimes malfunctions. Instead of adopting the specific structural form needed to do its job, it misfolds and begins to cluster, creating toxic, thread-like structures known as amyloid fibrils. In the case of Parkinson’s Disease, these protein deposits are referred to as Lewy-bodies.
The new study examined mutated forms of alpha-synuclein which have been found in people from families with a history of Parkinson’s Disease. In all cases, these mutations involved just one change to the protein’s amino acid sequence.
Although the differences in the sequence are small, the researchers found that they can have a profound effect on how quickly or slowly fibrils start to form. They also found that the mutations strongly influence a process called “secondary nucleation”, in which new fibrils are formed, in an auto-catalytic manner, at the surface of existing ones and thus enable the disease to spread.
The study stresses that these findings do not explain why humans get the disease. Parkinson’s Disease does not always emerge as a result of the mutations and has multiple, complex causes, which are not fully understood.
Image: Image of “amyloid fibrils”; thread-like structures which form after the protein alpha-synuclein aggregates. Plaques (protein deposits) consisting of this protein have been found in the brains of Parkinson ’s Disease patients and linked to disease.
Credit: Patrick Flagmeier
Reproduced courtesy of the University of Cambridge